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Inflammation Directs Memory Precursor and Short-Lived Effector CD8+ T Cell Fates via the Graded Expression of T-bet Transcription Factor
Open accessAbstract
As acute infections resolve, effector CD8(+) T cells differentiate into interleukin-7 receptor(lo) (IL-7R(lo)) short-lived effector cells (SLECs) and IL-7R(hi) memory precursor effector cells (MPECs) capable of generating long-lived memory CD8(+) T cells. By using another SLEC marker, KLRG1, we found that KLRG1(hi) effector cells began appearing early during infection and were committed to downregulating IL-7R. Unlike IL-7R(hi) MPECs, KLRG1(hi) IL-7R(lo) SLECs relied on IL-15, but IL-15 could not sustain their long-term maintenance or homeostatic turnover. The decision between SLEC and MPEC fates was regulated by the amount of inflammatory cytokines (i.e., IL-12) present during T cell priming. According to the amount of inflammation, a gradient of T-bet was created in which high T-bet expression induced SLECs and low expression promoted MPECs. These results elucidate a mechanism by which the innate immune system sets the relative amounts of a lineage-determining transcription factor in activated CD8(+) T cells and, correspondingly, regulates their memory cell potential.
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“Ag-specific CD8 T cells derived from the effector phase of a response can express various combinations of CD127 and KLRG1, which define either more short-lived effector cells (SLECs; CD127−KLRG1+), which are lost during the contraction phase of the immune response, or memory precursor effector cells (MPECs; CD127+KLRG1−), which are more likely to persist and contribute to memory populations [224,”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [225]
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Cites
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“…on the attribute examined, differ according to their localization, effector functions or potential to become protective memory CD8 T cells (de Bree et al., 2005; Huster et al., 2004; Kaech et al., 2003; Sallusto et al., 1999; Schluns et al., 2000; Voehringer et al., 2001; Wherry et al., 2003).”
BackgroundA Novel Transcription Factor, T-bet, Directs Th1 Lineage Commitment
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“…on the attribute examined, differ according to their localization, effector functions or potential to become protective memory CD8 T cells (de Bree et al., 2005; Huster et al., 2004; Kaech et al., 2003; Sallusto et al., 1999; Schluns et al., 2000; Voehringer et al., 2001; Wherry et al., 2003).”
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“The “decreasing potential model” for the development of memory CD8 T cells suggests that “memory T cells can only arise under conditions in which the antigenic load is limited and the stimulation of precursors ceases before a point of no return” (Ahmed and Gray, 1996).”
BackgroundInterleukin-7 mediates the homeostasis of naïve and memory CD8 T cells in vivo
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Th17: An Effector CD4 T Cell Lineage with Regulatory T Cell Ties
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Differentiation of Effector CD4 T Cell Populations
Zhu, J., Yamane, H., & Paul, W. E. (2010) · Annual Review of Immunology · doi:10.1146/annurev-immunol-030409-101212 · Cited by 3,452
Molecular Signature of CD8+ T Cell Exhaustion during Chronic Viral Infection
Wherry, E. J., Ha, S.-J., Kaech, S. M., Haining, W. N., Sarkar, S., Kalia, V., Subramaniam, S., Blattman, J. N., Barber, D. L., & Ahmed, R. (2007) · Immunity · doi:10.1016/j.immuni.2007.09.006 · Cited by 2,103
Self-citationDefining CD8+ T cells that provide the proliferative burst after PD-1 therapy
Im, S. J., Hashimoto, M., Gerner, M. Y., Lee, J., Kissick, H. T., Burger, M. C., Shan, Q., Hale, J. S., Lee, J., Nasti, T. H., et al. (2016) · Nature · doi:10.1038/nature19330 · Cited by 2,070
A human memory T cell subset with stem cell–like properties
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CD8 T Cell Exhaustion During Chronic Viral Infection and Cancer
McLane, L. M., Abdel-Hakeem, M. S., & Wherry, E. J. (2019) · Annual Review of Immunology · doi:10.1146/annurev-immunol-041015-055318 · Cited by 2,054
Metadata
- Authors
- Joshi, N. S., Cui, W., Chandele, A., Lee, H. K., Urso, D. R., Hagman, J., Gapin, L., & Kaech, S. M.
- Affiliations
- Yale University (US)
- National Jewish Health (US)
- Corresponding author
- Kaech, Susan M.
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2007-08
- Volume
- 27
- Issue
- 2
- Pages
- 281-295
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC2034442
- OpenAlex
- W1985294654
- Cited by
- 1,861
- References
- 50
- Citations by year
- 2026: 77 · 2025: 99 · 2024: 94 · 2023: 112 · 2022: 108 · 2021: 137 · 2020: 125 · 2019: 105 · 2018: 99 · 2017: 73 · 2016: 105 · 2015: 110 · 2014: 106 · 2013: 117 · 2012: 102
- FWCI
- 25.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Wellcome Trust
- National Institute of Allergy and Infectious Diseases (P01AI022295, R01AI057485, R01AI054661, P01 AI22295, T32AI055403, R01AI056322, R01AI066232)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- CD8+ T cells, short-lived effector cells, memory precursor effector cells, T-bet, IL-7 receptor, KLRG1, IL-15, IL-12, inflammation, T cell differentiation, memory T cell generation, innate immune regulation
- MeSH terms
- T-bet Transcription Factor, Animals, Immunologic Memory, Infections, Inflammation, Interferon-gamma, Mice, Mutant Strains, Receptors, Immunologic, Biomarkers, Cytokines, CD8-Positive T-Lymphocytes, Interleukin-12, Interleukin-15, Receptors, Interleukin-7, T-Box Domain Proteins, Lectins, C-Type, Mice
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